A high Bacteroides/Clostridium ratio is associated with the ability of male gut microbiota transplants to suppress lupus in female BWF1 mice

Abstract

Systemic lupus erythematosus (SLE) is associated with microbiota dysbiosis. Our experiments conducted from 2014–16 using NZBxNZW F1 (BWF1) mice showed that gut microbiota composition differed between adult female and male mice, and male cecal transplants into female mice suppressed disease. In 2017, our BWF1 colony was moved to a new campus facility with identical water, food and bedding. Although disease incidence/kinetics were similar between the two facilities, male cecal transplants could not suppress disease in female recipients in the new facility. Several changes were made in 2018, including water source, rooms in the facility and disinfecting procedures. Transplant experiments conducted after the changes (2019–2020) recapitulated the results from our original animal facility, i.e., male cecal transplants could suppress disease in female mice. Microbiota composition in female and male BWF1 mice was compared for the three different periods. We found that Bacteroides abundance was high in male mice, and Clostridium was very low during the periods when male cecal transplants suppressed disease. Alistipes was also present during periods when male cecal transplants worked, and absent when they did not work. These same patterns were also found in females receiving male cecal transplants, with a high Bacteroides/Clostridium ratio and Alistipes presence correlating with disease suppression. These data suggest that Bacteroides and Clostridium may have opposing effects on disease suppression that may also require the presence of Alistipes. Our findings further highlight how changes in environmental conditions can have dramatic effects on microbiota composition that can directly influence the immune response and disease.